Efeito protetor do lipopolissacarídeo da Escherichia coli na lesão gástrica por indometacina em ratos : envolvimento da cicloxigenase do tipo 2, da no sintase induzida e dos canais de potássio sensíveis ao ATP

Abstract

The role of the LPS in the defense of the gastric mucosa is still not established. AIMS: 1-To verify the protective effect of the LPS in the gastric damage (GD), in the neutrophil infiltration (NI), in the increase of the leukocyte of adhesion, in the reduction of the induced glutathione levels for indomethacin (INDO) in rats; 2- To investigate the role of the COX-2, NOSi and of ATP-sensitive k channels (KATP) in the protective effect of LPS administration on INDO- induced gastropathy. METHODS: The rats were treated with LPS of E. coli (30, 100 or 300 mg/Kg, e.v.). After 6 hs, INDO was administrated (20mg/Kg, p.o.). Three hs later, the blood was harvested for determination the total and differential number of white blood cell counts. Later, the rats had been sacrificed and the GD was surveyed. Piece of the stomach had been removed for evaluation of the myeloperoxidase (MPO) activity and determination of the glutathione (GSH) levels. The adhesion and rolling of the leukocytes had been evaluated by intravital microscopy. Different groups were treated with rofecoxib, L-NAME, aminoguanidine, dexamethasone, glibenclamide, diazoxide or glibenclamide + diazoxide. After 3 hs of the administration of INDO (20mg/Kg, p.o.), had been evaluated the GD, MPO and GSH. RESULTS: LPS reduced dose- dependently INDO- induced GD and increase in MPO, with the maximal effect at the dose of 300 g/kg and in the time of 6 hs. The LPS treatment neutrophilia induced in INDO induced gastropathy. LPS reverted to the fall of the GSH levels in the stomach with INDO. The LPS treatment decreased the adhesion and increased rolling of the leukocytes when compared with the INDO treated. Rofecoxib, L-NAME, aminoguanidine or dexamethasona had not reverted the protective effect of the LPS. Glibenclamide, but not diazoxide, reverted the protective effect of the LPS in the induced gastropathy for INDO, increasing of significant form the GD, MPO and decreasing the GSH. The diazoxide + glibenclamide association of with did not revert the protective effect of the LPS. CONCLUSIONS: LPS protects against INDO induced GD, through the inhibition of the NI for a reduction of the adhesion of leukocytes to the endothelin and for an increase of the GSH levels in the stomach. This dependent event of the KATP opening. Our data also suggest that the activity of COX-2 and NOSi are not involved in the protective effect of the LPS.